Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4 M and K4 M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation,ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels.Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4 M and K4 M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials.The ionic concentration strength of the media was also varied over a range of 0-0.4 M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm.The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system.The particle shape analysis showed the HPMCK4 M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4 M polymer, possibly a contributory factor to the gelation process.The results showed gelation occurred quicker for the K4 M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4 M tablet matrices. Theionic strength also had more of an effect on the drug release from the E4 M matrices. The experiments highlighted the resilience of the K4 M matrices in comparison with the E4 M matrices. The results thus show that despite similar viscosities of E4 M and K4 M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices.